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Biomedical subjects

P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 91 records · Page 5Linked to original sources

Epidemic Pseudomonas aeruginosa serotype O16 bacteremia in hematology-oncology patients.

From 1 August 1978 through 31 December 1982, 98 hematology-oncology patients had positive cultures for Pseudomonas aeruginosa serotype O16; 22 of these patients developed bacteremia, and this bacteremia was associated with the occurrence of extensive perineal cellulitis in 10 patients (45.5%). Seventeen bacteremic patients died. The epidemic strain differed from other P. aeruginosa organisms isolated at the hospital by its resistance to all antibiotics available at that time (ticarcillin, piperacillin, azlocillin, tobramycin, ceftizoxime, ceftriaxone, moxalactam, ceftazidime, and fosfomycin). Univariate analysis showed the following factors to be significantly associated with P. aeruginosa O16 bacteremia: the severity of granulocytopenia at the time of the bacteremia, more days with fever, the administration of ticarcillin or an aminoglycoside, the receipt of a greater number of antimicrobial agents for a longer period of time before documentation of the bacteremia, and the occurrence of cellulitis. Logistic regression analysis showed that duration of fever, duration of bacteremia, and the number of antimicrobial agents administered before documentation of the bacteremia were the best predictors of P. aeruginosa O16 bacteremia. In a prospective study of the acquisition of P. aeruginosa by hematology-oncology patients, 1,149 specimens (throat and rectal swabs) from 270 patients and 201 specimens from their washbasin drains were collected. On only three occasions was the epidemic strain isolated from both the patient and his or her washbasin, but in each case the colonization of the patient preceded the isolation of the strain from the washbasin. The transmission of any P. aeruginosa organism from washbasin drain to patient could not be documented. Contact isolation precautions from the Centers for Disease Control were used for all hematology-oncology patients colonized or infected with P. aeruginosa after 7 January 1983. No case of P. aeruginosa O16 bacteremia has occurred at Hotel Dieu since July 1984.

Adult↗

Relapses after stopping chemotherapy for experimental tuberculosis in genetically resistant and susceptible strains of mice.

Three strains of mice (Swiss albinos, C57BL/6,C3H/OuJ) were injected intravenously with 3.7 x 10(6) colony forming units (CFU) of M. tuberculosis, H37RV, sensitive and resistant to antibiotics (90% of bacilli sensitive, 9% resistant to Streptomycin and 0.9% resistant to Kanamycin). Two weeks later, chemotherapy was started 6 days a week for a 6-month period with isoniazid (INH) and rifampicin (RMP). Twenty mice of each strain were killed at the end of the chemotherapy and the others were kept without antibiotics for a second 6-month follow-up period before being killed. The early multiplication of bacilli during the first 2 weeks following infection and before chemotherapy, was similar in the three strains of mice. Chemotherapy had the same apparent efficacy in the three strains of mice, nearly all the mice being cured as assessed by a negative spleen culture on Loewenstein-Jensen medium at the end of chemotherapy. But after the 6-month follow-up period, the C3H strain presented a statistically significantly higher level of positive spleen culture ('relapse') than seen in the C57BL/6 strain, and an increased number of mycobacteria per relapsing mouse spleen. It has been estimated with the help of resistant and sensitive bacilli that the relapses were due in most of the cases to the regrowth of one or very few bacilli, giving a clone. It seems that the C3H strain of mice, known to carry the Bcg-r allele of the Bcg gene, might be less able to develop a specific acquired resistance capable of stopping the delayed development of a highly virulent strain of mycobacteria.

Animals↗

The stability and immunogenicity of a dispersed-grown freeze-dried Pasteur BCG vaccine.

The level of antituberculous immunity seems to be related to the number of memory T cells induced. This may vary as a function of the multiplication and persistence of BCG in host tissues. The most important requirements for a BCG vaccine are, therefore, the immunogenicity of the strain, the high proportion of live to dead bacilli, and adequate dispersion and low levels of soluble antigens. The surface-grown Pasteur BCG vaccine contains a very high proportion of bacilli killed by ball-milling and freeze-drying. It also contains clumps and soluble antigens, all factors influencing cell-mediated immune processes and viability control. Therefore, several batches of vaccine were prepared on an industrial scale using one of the most immunogenic strains (French 1173 P2) and grown as dispersed bacilli by a modified cell type culture method. This method provided fully viable, well-dispersed vaccines which have a viability and heat stability superior to that of the classical surface-grown BCG. The immunogenicity was checked by multiplication and persistence in mouse organs and the skin reactivity and tuberculin hypersensitivity in guinea-pigs showed results comparable to those obtained with classical vaccine. Small-scale tests in children showed superior immunogenicity of the dispersed as opposed to the classical vaccine and there was no suppurative adenitis.

Animals↗

Comparative in vitro activities of pristinamycin, its components, and other antimicrobial agents against anaerobic bacteria.

Using an agar dilution technique, we compared the activities of pristinamycin and its components PIA and PIIA with those of penicillin G, cefoxitin, chloramphenicol, metronidazole, and clindamycin against 200 strains of anaerobic bacteria isolated from suppurative lesions. The antimicrobial activity of pristinamycin was similar to that of chloramphenicol. On the basis of these results and because of its antistaphylococcal and antistreptococcal activities and its absence of toxicity, pristinamycin might be a valuable therapeutic agent for treating mixed aerobic-anaerobic cutaneous infections.

Bacteria, Anaerobic↗

Lysis centrifugation and slide blood culture systems for diagnosis of bacteremia in immunocompromised patients.

Compared with a slide blood culture system, a lysis centrifugation system detected significantly more positive blood cultures and more episodes of bacteremia in immunocompromised patients (even when on antibiotics), while giving results more rapidly and even at significantly lower CFUs. However, it had a high contamination rate and did not detect Pseudomonas aeruginosa as often. Use of the two systems together is recommended for diagnosing bacteremia early in immunocompromised patients.

Agranulocytosis↗

[Bacteria, host defense mechanisms and antibiotics].

If immunopharmacological studies of antibiotics have to be done, it urgently involves the development of a better knowledge of the relationships existing between the bacterial virulence factors, the non specific and specific host defense mechanisms and the antibiotics. This will lead to a better and deeper analysis of the antibiotics immune targets at the cellular and molecular levels and will produce and validate new in vivo and ex vivo experimental models, being standardized and closed to clinical setting. These two conditions would permit a better choice of antibiotics in infected patients, taking into account all the factors needed for the recovery.

Anti-Bacterial Agents↗

[Effect of various antibiotics on granulopoiesis, in mice treated with cyclophosphamide, in an in vivo model of experimental C. albicans infection].

The effect of piperacillin (PIP), cefotaxime (CTX), cefoxitin (CXT) on the natural resistance to C. albicans infection has been evaluated in vivo, in normal or neutropenic mice, in correlation with the PMN count in the peripheral blood. In neutropenic mice treated with PIP or CTX, the number of PNN increased more rapidly and higher than in CXT treated or control mice. A dose dependent increased resistance to infection was observed in PIP treated mice. It did not parallelled the PMN level found in different group of mice. The explanations might be a decrease of functional activity of PMN and/or an increase proliferation and differentiation of others effector cytotoxic cells.

Animals↗

[Action of immunostimulants on phagocytosis and derivative actions].

One of the main objectives of immunopotentiators is their ability to enhance or to restore natural anti-infectious resistance of normal or immunocompromised hosts. Numerous experimental resistance models have been used in screening such potentiators. However, once such a substance has been selected, its potential and practical use will directly depend on the knowledge of the underlying resistance mechanisms induced, defining its cellular or molecular targets. Phagocytosis-polymorphonuclear or monocyte-macrophage dependent--is the most frequently described variable which have been analysed among the various potentially active mechanisms of non-specific resistance. Various in vivo and in vitro tests might be used and the target of several immunostimulants among the different steps of phagocytosis are described. However, numerous intrinsic limitations are associated with such tests and news models or tests are presented and discussed in order to gain more insights into the evaluation of active substances.

Adjuvants, Immunologic↗

Various strains of BCG vaccine and genetic control of the immune response of mice.

Numerous field trials of BCG vaccine, undertaken to evaluate its effectiveness in the prophylaxis of human tuberculosis, indicated that the levels of protection achieved were not uniform. Most probable factors influencing these results are: partial protection due to atypical mycobacteria, tuberculosis expectancy in different population, nutritional and socio-economic factors, potency of BCG vaccines, and genetic factors controlling the host immune response. Specific and non specific hallmarks of cell-mediated immunity after BCG infection were analysed in various outbred, inbred and recombinant lines of mice, testing the capacity of different preparations and strains of BCG vaccine. Results of such studies did show that the by far most important factor involved the type of immune response related to gene(s) controlling the natural resistance and the expression of C.M.I. Consequences for future mass and individual BCG vaccination as well as the proper integration of BCG vaccination in antituberculous policy are discussed.

Animals↗

Effects of suramin on the in vivo antimicrobial resistance against Listeria monocytogenes and Mycobacterium bovis (BCG) in mice.

Following one intraperitoneal injection of Suramin (400 mg/kg) in mice, biphasic alterations of the resistance to Listeria monocytogenes were observed, depending on the timing of the drug administration in relation to the intravenous challenge. Treatment with suramin, concomitantly or 1 day before, enhanced markedly the bacterial growth in spleen and liver, detected as early as 3 to 6 h after the challenge, the maximum being observed at 48 h in the liver. In contrast, an increased resistance was observed when suramin was given 8 days before the challenge. This late effect was associated with a stimulation of the mononuclear phagocyte system as measured by the increase of the spleen index and accumulation of histiocytic cells in the lymphoid organs, such as peripheral nodes. Intraperitoneal inoculation of suramin (100 mg/kg), before, during and after an intravenous injection of low dose (2 X 10(4)/mouse) of Mycobacterium bovis (BCG) in C57BL/6 and CH3 mice were followed, in both strains, by a similar increase of the mycobacterial growth in spleen and liver during the first 2 weeks. This indicates that suramin was acting on a different non specific mechanism of resistance than the one being expressed by the Bcg gene controlling the natural resistance as described recently. However, when the same schedule of suramin treatment was given to these two strains, during subcutaneous immunization with 1 X 10(7) viable BCG, a significant decrease of 48 h delayed-type hypersensitivity to tuberculin was noted 21 days later only in C57BL/6 but not in C3H mice, in which such a reaction was also of low magnitude in the infected control. The decrease of this cell-mediated immunity parameter in C57BL/6 suramin treated mice was also correlated with a higher number of viable BCG found at the challenge site and in the draining nodes.

Animals↗

Strain variation of lymphokine production and specific antibody secretion in mice infected with Mycobacterium lepraemurium.

Mice from strains showing either phenotypical expression of Bcg gene (C57BL/6, BALB/c, DBA/1, and (C57BL/6 X DBA/2)/F1, CBA, A/J, DBA/2) were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). The number of acid-fast bacilli (AFB) within the spleens, the ability of spleen cells to produce in vitro interleukin 1 and 2, and the serum levels of specific anti-MLM antibodies were assessed 3 months later. The number of AFB recovered from the spleens of various strains followed the strain distribution of genetically controlled innate resistance established for Mycobacterium bovis infection. A decrease of interleukin 2 production by spleen cells could be detected in C57BL/6, DBA/1, DBA/2 and (C57BL/6 X DBA/2)F1 mice only. The level of anti-MLM antibodies was found to be higher in C57BL/6, BALB/c and A/J mice than in the other strains tested. Thus no evidence appeared of a direct influence of the Bcg gene on lymphokine production and antibody secretion.

Animals↗

Detection of bacteremia in leukemic patients by early subcultures with a slide blood culture system.

During a three month study, 433 sets of blood culture were collected from 140 patients hospitalized in the hematology unit, most of these blood cultures were collected from leukemic patients being treated by chemotherapy producing aplasia. Blood was distributed into three bottles, one containing Schaedler Broth and the others tryptic soy broth (TS). We tried to compare two different blind subculture systems: conventional subculture (CS) onto Petri dishes chocolate agar and a coated agar slide (slide) attached onto the TS bottle, thus the blood culture broth can be subcultured by tipping the bottle. The first subculture was performed at the same time for both bottles after a mean time of incubation of 12,4 hours (st. dev. 3.3 hours). There was no statistically significant difference for the recovery of pathogens, 30 with the slide and 29 with CS. Among the 30 slide positive blood cultures, six: 4 pseudomonas, 2 streptococcus, were detected by direct observation of colonies before any evidence of broth disturbance. When comparison was made according to the detection observed with the first, second or third subculture, a slight advantage was obtained with CS since 72.4% of them were positive with the first subculture versus 60% with the slide. During the first round of evaluation an higher contamination rate was observed with the slide 6.4% versus 2% for CS. The great majority of contaminated bottles were collected in one of the three hematology subunits. Contamination rate dropped following a teaching campaign bout aseptic collection and distribution of blood into the bottles.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriological Techniques↗

Influence of dose and route of Mycobacterium lepraemurium inoculation on the production of interleukin 1 and interleukin 2 in C57BL/6 mice.

Groups of C57BL/6 mice were infected either intravenously or subcutaneously with 10(5) or 10(8) Mycobacterium lepraemurium cells, and the ability of their splenic macrophages and T-cells to produce, respectively, interleukin 1 on lipopolysaccharide stimulation and interleukin 2 on concanavalin A stimulation was assessed during the course of infection. In all groups of infected mice, interleukin 1 production remained unaffected during the entire observation period, whereas interleukin 2 activity decreased as the infection progressed. Heavily infected mice (10(8) M. lepraemurium cells) showed an earlier and stronger deficiency interleukin 2 production by concanavalin A-stimulated spleen cells than did mice infected with a lower dose (10(5) bacilli), without detectable influence by the route of inoculation. In mice receiving 10(5) bacilli, minor differences were seen according to the route of infection, with a slight delay in interleukin 2 decrease in mice injected intravenously. In subcutaneously inoculated mice, the failure of spleen cells to produce interleukin 2 after concanavalin A stimulation did not correlate with the number of bacilli developing in the spleen, suggesting the existence of suppressor mechanisms acting at a distance from the site of inoculation.

Animals↗

Preliminary evidence of natural resistance to Mycobacterium bovis (BCG) in lepromatous leprosy.

An assay system has been developed based on radiometric quantification of 3H uracil incorporation into viable BCG in the absence or presence of blood monocytes in cultures from untreated lepromatous (LL) or tuberculoid (TT) leprosy patients. 3H Uracil incorporation into BCG was inhibited when the bacilli were cultivated in the presence of blood-derived macrophages in culture for four days, and that inhibition was always greater with macrophages harvested from LL patients compared to TT patients. The reasons for such an observed difference in humans are discussed according to our knowledge obtained in murine models of mycobacterial infections.

Adult↗